Objectives: 1. Continuing effort will be made to study the structure of synthetic short helices of nucleic acid and tRNA by NMR. In view of the new addition of the NMR spectrometer providing capability for measurement of C13 NMR properties, significant progress in this area is anticipated in the coming year. Much effort will also be devoted to the study of interaction of the helical nucleic acid with mutagens and carcinogens in aqueous solution. Considerable challenge in synthesis has to be met in order to launch this program. 2. Great effort will be made to extend the oligonucleotide ethyl phosphotriester studies. In this work, specific oligonucleotides complementary to the sequence in tRNA and to the poly A section of the messenger RNA will be made. Physicochemical, biochemical, and biological studies will be made on the interaction of these specific oligonucleotides with the complementary portion of nucleic acid in solution or with the living cell. 3. Effort will be made to investigate the structure and function relationship of poly I-poly C as interferon inducer. Modification of the backbone by substitution of 2'-O-methyl derivatives has yielded very interesting results and will be continued.